Renal haemodynamic effects of B-2 receptor agonist bradykinin and B-2 receptor antagonist HOE 140 in conscious lambs

The present study was designed to test the hypothesis that the high renal v ascular resistance characteristic of the newborn results from age-dependent changes in the responsiveness of the renal vasculature to kinins. Two stud ies were carried out in conscious, chronically instrumented lambs aged 1 an d 6 weeks. Firstly, we measured the renal blood flow response to intra-arte rial injection of the B-2 receptor agonist bradykinin over the range of dos es 0-800 ng kg(-1). The ED50 renal blood flow response to bradykinin was 50 ng kg(-1) in both age groups of lambs. Secondly, we measured the effects o f intravenous administration of 12.5 mug kg(-1) of the specific B-2 recepto r antagonist HOE 140; this dose attenuated the renal blood flow response to 50 ng kg(-1) of bradykinin in both age groups. HOE 140 administration was associated with an age-dependent increase in mean arterial pressure, with l ittle effect on heart rate or renal vascular resistance. This study provide s new information regarding the effects of kinins in modulating renal haemo dynamics during postnatal maturation. We reject our hypothesis and conclude that the high renal vascular resistance of the newborn does not appear to result from age-dependent changes in the responsiveness of the renal vascul ature to endogenous kinins.